The [R]Evolutionary Work of a Leading Scholar

One of the world's foremost classical evolutionary biologists says he likes
to work on the "neglected problems" of the field.

By Scott Hauser

EVOLUTION OF A BIOLOGOY TEACHER: Allen Orr was a philosophy
major at the College of William and Mary when, as a junior,
he took an evolution course. He soon added biology as a double
major and has not looked back.

At Rochester, Orr frequently teaches the upper-level undergraduate
course on evolution, and although there is no evidence that
he's yet persuaded any philosophy majors to add biology to
their coursework, he has been recognized as an excellent teacher.

In April, students voting in the annual College Students'
Association "Professor of the Year" competition
chose Orr as the best professor teaching in the sciences.

In an age when molecular biology has defined most species right down to the
base pairs of their DNA, H. Allen Orr prefers the classical comfort of the tried
and true fruit fly.

The tiny insect, better known to most as a habitué of garbage cans,
has long been the Ford Fairlane of genetics-a fine vehicle, to be sure, but
not terribly glitzy.
But for Orr, one of the world's leading practitioners of classical genetics
in its modern form, the minute members of the Drosophila genus that fill
a wall of storage units in his laboratory have been the source material for
extraordinarily broad insights into the biological mechanics of adaptation and
speciation.

Over the past decade, the one-time philosophy major turned Rochester biology
professor has been quietly altering notions that many in evolutionary biology
had thought were resolved more than half a century ago.

"I like to work on the neglected problems, the ones nobody else seems
to be exploring," Orr says. "For the past 50 years or so, up until
the late 1980s, speciation was pretty much an intellectual backwater in evolutionary
biology. It really just got left behind."

"Adaptation was pretty dead, too," he says. "You think of adaptation
as the name of the game in evolution, but it had become neglected because everybody
thought they knew the answer."

Neither speciation-the study of how one species branches off to become a separate
species-nor adaptation-the evolutionary process by which organisms become best
suited to their environments -are backwaters now, thanks to Orr.

Over the last five years, he has presented and honed a new explanation of adaptation,
the first such postulation in the past 70 years, tweaking the work of one of
the giants in evolutionary biology, R. A. Fisher. In other work, Orr has proposed
what's considered an unusually elegant solution to a problem first identified
by the great British scientist J. B. S. Haldane: Namely, why is it that when
two species cross, the male offspring are more likely to be infertile than the
female offspring?

Orr and his former Ph.D. advisor Jerry Coyne of the University of Chicago are
credited with re-energizing the field of speciation with their late 1980s analysis
of how species of Drosophila become separate from one another. Their
work is so well known that their most-cited paper, "Patterns of Speciation
in Drosophila," made a cameo appearance in last year's David Duchovny movie
Evolution.

That's quite a buzz for a specialist whose experimental methods are, at heart,
unchanged from the mid-19th century when Gregor Mendel first mapped out the
fundamentals of heritable traits by crossbreeding pea plants.

Much in biology has changed since then, of course. Most notably, advances of
molecular biology have allowed scientists to see ever finer detailed pictures
of the mechanics behind genetics.

By the time Orr began pursuing his Ph.D. in the 1980s, the focus of most evolutionary
biologists had moved to mapping chromosomes, genes, and DNA. The fruit fly had
lost some of its luster.

"The molecular biologists had taken over," says Coyne, who admits
he took Orr into his lab on the less-than-wholehearted recommendation of their
common mentor, biologist Bruce Grant of the College of William and Mary. "He
is what we would call a classical evolutionary biologist. As am I."

Working together, Coyne and Orr have provided the field's most compelling analysis
for estimating how and when one species branches off to become a separate species.
Their 1989 paper (updated in 1997) analyzing the genetic changes that take place
in crosses of fruit flies has given evolutionary biologists a breakthrough tool
for understanding the process.

One of the principal phenomena of evolution, speciation is a neverending process
that, although it occurs on the order of hundreds of thousands of years, continues
apace. Biologists consider a new species to have been established if members
of the new species can no longer mate with members of their parent species.
They either refuse to do so (or cannot because of geography), or when they do
mate, their offspring are sterile or stillborn.

A Critical Viewpoint

When he needs a break from speciation and adaptation, Allen Orr
likes to write critical essays, often book reviews for the Boston
Review, on the intellectual currents in his field and among
evolution's critics.

"I like to have some breadth," Orr says. "I like
working on a range of problems."

"And it gives me a chance to flex some of my old philosophy
muscles."

While Orr says he has no plans to become a full-time scientific
essayist writing for a lay audience such as the late Stephen J.
Gould, E. O. Wilson, or Richard Dawkins, he does feel compelled
to take up the pen to engage evolution's critics, in particular
scientific creationists and proponents of "intelligent design,"
the notion that life on Earth is so unique that it had to have had
some non-Earthly source to jumpstart it.

"I'm a second stringer when it comes to battling these guys,"
Orr says. "But I think it is important for evolutionary biologists
to engage these guys in battle."

He notes the irony of evolution's status in popular culture.

"Evolution is in a strange position," he says. "It's
probably the one science that simultaneously has the best public
spokespeople and the best popular books written by outstanding people
like Gould, Wilson, and Dawkins.

"I don't think there is any field that is blessed with such
superb popularizers," he says. "And yet we're the most
misunderstood field."

While speciation attracted a lot of interest from scientists after Darwin first
identified natural selection in 1859, the topic had faded from the front burner
in the 20th century until Coyne and Orr resuscitated it.

Coyne, a professor in Chicago's Department of Ecology and Evolution, is quick
to point out that while Orr may work in classical genetics, he is anything but
old-fashioned in the way he approaches his work.

He is something of a modern hybrid unto himself, making major contributions
to his field as an experimentalist and as a theoretician who can find connections
across areas of evolutionary biology, Coyne says. When his interests have taken
him in new directions that have required new skills, Orr has plunged right in.

He's a polymath," Coyne says. "And he's an autodidact when it comes
to mathematics. The adaptation work, in particular, requires a complex mathematical
armament, and he taught himself the tools that he needed.

"I've never seen a person enter a field and take it over the way he has,
considering where he was when he began."

Orr begins most of his groundbreaking work where classical geneticists have
long launched their studies-in a lab full of fruit flies. His Hutchison Hall
laboratory is stocked with several varieties of Drosophila, including
the run-of-the-mill kind that crashes picnics as well as several exotic species
from Asia and the Pacific.

The three-millimeter long insects are ideal for experiments that require analyses
across generations because a fertile pair can produce offspring in about two
weeks. As an added scientific benefit, the insects have only four pairs of chromosomes
(as opposed to the 23 pairs found in humans), and their genome is only about
165 million base pairs long, containing about 14,000 genes. (The human genome
contains about 3 billion base pairs and about 70,000 genes.)

"They're cheap, they're quick, and you can get them in huge numbers,"
Orr says. "They're easy live animals."

Orr's laboratory team crosses members of the species with different characteristics-such
traits as white eyes or curly wings-puts them together in flasks and lets nature
take its course. Two weeks later, he and the members of his lab have a new generation
of flies.

They then selectively separate the offspring and breed them again until they
have flies that consistently display a chosen set of characteristics. By examining
the genes of the crossbred flies, they can identify which and how many genes
are involved in each generation's divergence.

"In that sense, it's pretty low-tech science," Orr says.

But the analyses are not.

In his work on adaptation, Orr challenges what has come to be known as the
"micromutational view"-Fisher's notion that evolution is driven by
lots of small, random mutations that each have the same 50-50 chance of contributing
to species survival.

"That's really been gospel for 70 years or so," Orr says. "Now,
there's a group of us questioning that."

The more Orr questioned, the more he realized that the facts didn't seem to
fit the theory. Instead of marching in a relatively steady line from one spot
to another on an evolutionary path, species in nature frequently did not diverge
through a concatenation of a lot of small changes. As Orr analyzed the data,
he discovered that sometimes very large genetic changes occur, making the path
to the environmental optimum more exponential than linear.

"What I wanted to ask is, Are there genes of very large effect?"
Orr says. "Are there real whoppers? Are there single genes that if you
put them on a genetic background, would they cause hybrid sterility or hybrid
inviolability? And the answer is, sometimes, yes."

It was an "Ah-ha" moment that Orr remembers well, but he also remembers
the harder part: "Once I realized that, it was a long slog of doing computer
simulations and a little bit of algebra to figure out what the answer is. That
took more than a year."

Orr now is trying to re-create his prediction at the molecular level, and so
far, the predictive power holds.

"I think this is a very robust model."

How does he feel taking on a giant in the field like Fisher?

"It's easier to do something like that if you are working on ignored problems,"
Orr says. "It's just that nobody has worried about this for the past 70
years.

"I don't want to take anything away from Fisher," Orr says. "He
got most things right. He just misinterpreted the math."

The approach of looking at neglected problems will continue, he says.

"My lab tries not to do what everybody else is doing," Orr says.
"We're consciously trying not to work on things that everyone else is working
on."

As for Orr, he planned to finish a book this summer on speciation that he has
been writing with Coyne. The first full volume written on the subject in decades,
the book will summarize the developments over the past decade-several of them
their own.

"Speciation is actually getting kind of crowded right now," Orr says
with a look that indicates he's on the lookout for another challenge. "Adaptation
has a little more elbow room."